产品描述
SB-431542, a small molecule inhibitor of the type I TGF-β receptor, blocks intracellular mediators of TGF-1 signaling, which leads to decreased TGF-β1–mediated proliferation, cytokines and collagen expression. In clinical settings, SB-431542 is widely used to treat respiratory asthma, and inhibits proliferation and synthesis of adventitial fibro in the process of pulmonary vascular remodeling.[1]
In vitro study indicated that SB-431542 is able to inhibit ALK5 with an IC50 of 94 nM and other type I receptors, such as ALK4. Although SB-431542 inhibited ALK4 with an IC50 of 140 nM. Moreover, SB-431542 inhibited TGF-β1–induced collagen Iα1 and PAI-1 mRNA with IC50 values of 60 and 50 nM, respectively. In addition, SB-431542 inhibited TGF-β1–induced fibronectin mRNA and protein with IC50 values of 62 and 22 nM, respectively. These data demonstrate for the first time that ALK5 activity is required for TGF-β1 regulation of extracellular matrix markers FN, collagen Iα1, and PAI-1 mRNA.[1]
In vivo study demonstrated that SB-431542 has the capacity to inhibit TGF-β1-induced gene expression. SB-431542 is recognized as a important inhibitor of the TGF-β1 receptors in blocking TGF-β1/Smads signal pathways in vascular remodeling. Moreover, hypoxia-induced vascular remodeling can significantly increase the amount of cytokines and collagen in vascular adventitia. However, after the treatment of SB-431542, attenuation of the fibrosis promoting effects of TGF-β1, including TGF-β1-induced cell proliferation, cell motility, cell migration and cell synthesis were observed. Therefore, it is significant to the identify the potential of SB-431542 for the treatment of hypoxia-induced pulmonary hypertension.[2]
References:
[1]. Laping NJ, et al. Inhibition of transforming growth factor (TGF)-beta1-induced extracellular matrix with a novel inhibitor of the TGF-beta type I receptor kinase activity: SB-431542. Mol Pharmacol. 2002 Jul;62(1):58-64.
[2]. Yuan W, et al. SB-431542, a specific inhibitor of the TGF-β type I receptor inhibits hypoxia-induced proliferation of pulmonary artery adventitial fibroblasts. Pharmazie. 2016 Feb;71(2):94-100.
SB-431542 是 I 型 TGF-β 受体的小分子抑制剂,可阻断 TGF-1 信号转导的细胞内介质,从而导致 TGF-β1 介导的增殖、细胞因子和胶原蛋白表达减少。在临床上,SB-431542被广泛用于治疗呼吸性哮喘,抑制肺血管重构过程中外膜纤维的增殖和合成。[1]
体外研究表明,SB-431542 能够以 94 nM 的 IC50 抑制 ALK5 和其他 I 型受体,例如 ALK4。尽管 SB-431542 以 140 nM 的 IC50 抑制 ALK4。此外,SB-431542 抑制 TGF-β1 诱导的胶原蛋白 Iα1 和 PAI-1 mRNA,IC50 值分别为 60 和 50 nM。此外,SB-431542 抑制 TGF-β1 诱导的纤连蛋白 mRNA 和蛋白质,IC50 值分别为 62 和 22 nM。这些数据首次表明,TGF-β1 对细胞外基质标志物 FN、胶原蛋白 Iα1 和 PAI-1 mRNA 的调节需要 ALK5 活性。[1]
体内研究表明,SB-431542 具有抑制 TGF-β1 诱导的基因表达的能力。 SB-431542 被认为是 TGF-β1 受体的重要抑制剂,可阻断血管重塑中的 TGF-β1/Smads 信号通路。此外,缺氧诱导的血管重塑可以显着增加血管外膜中细胞因子和胶原蛋白的数量。然而,在 SB-431542 处理后,观察到 TGF-β1 的纤维化促进作用减弱,包括 TGF-β1 诱导的细胞增殖、细胞运动、细胞迁移和细胞合成。因此,鉴定SB-431542治疗缺氧性肺动脉高压的潜力具有重要意义。[2]
Chemical Properties
Cas No. | 301836-41-9 | SDF | |
化学名 | 4-[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1H-imidazol-2-yl]benzamide | ||
Canonical SMILES | C1OC2=C(O1)C=C(C=C2)C3=C(NC(=N3)C4=CC=C(C=C4)C(=O)N)C5=CC=CC=N5 | ||
分子式 | C22H16N4O3 | 分子量 | 384.39 |
溶解度 | ≥ 19.2mg/mL in DMSO, ≥ 10.06 mg/mL in EtOH with ultrasonic | 储存条件 | Store at -20°C |
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while. | ||
Shipping Condition |
Evaluation sample solution : ship with blue ice All other available size: ship with RT , or blue ice upon request |
溶解性数据
制备储备液 | |||
1 mg | 5 mg | 10 mg | |
1 mM | 2.6015 mL | 13.0076 mL | 26.0152 mL |
5 mM | 0.5203 mL | 2.6015 mL | 5.203 mL |
10 mM | 0.2602 mL | 1.3008 mL | 2.6015 mL |
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